The roles of genetic, viral and immunologic components in the etiology of autoimmune diseases and malignant lymphomas in a murine model, the New Zealand (NZB) mice, is being analyzed. A sensitive quantitative assay demonstrated high titers of xenotropic type-C RNA virus production throughout life in all NZB mice. Genetic crosses made by breeding NZB mice with nonautoimmune strains that expressed little or no xenotropic virus showed that two independently segregating autosomal dominant loci (NZV1 and NZV2) determine virus expression. The virus inducing loci were not linked to H-2 type, coat color or sex. Autoimmune markers (direct Coombs' test, anti-DNA antibody, nephritis) appeared much later and only in a small proportion of mice among these crosses compared to the NZB parent. There was no significant difference in virus titers among the virus positive mice of these crosses who developed autoimmune disease as compared to their littermates who did not show any autoimmune markers. A large number of mice that expressed high titers of virus like the NZB parent did not develop any autoimmune disease even up to 18 months of age. Finally, a proportion of mice among those crosses that were virus negative on repeated testing developed autoimmune disease and nephritis. Therefore, genetic factors controlling the expression of virus and autoimmunity can be segregated and the development of autoimmunity in NZB mice and their crosses is independent of xenotropic virus expression. BIBLIOGRAPHIC REFERENCES: Datta, S.K. and Schwartz, R.S.: Susceptibility to lymphomas and expression of C-type RNA viruses during the graft-versus-host reaction. Europ. J. Cancer, 12:977-988, 1976. Levy, J.A., Datta, S.K. and Schwartz, R.S.: Recovery of xenotropic virus but not ecotropic virus during graft-versus-host reaction in mice. Clin. Immunol. Immunopath, 7:262-268, 1977.